3. Cell metabolism in brain cell cultures

(Dr G.J. McBean)

An NMR study of alanine and glutamate metabolism in astrocytes and nerve cells (Dr G McBean and Dr J.P.G. Malthouse)
Our interest in the pathways of glutamate metabolism stems from our observations that a number of gliotoxic amino acid derivatives (b-N-oxalylamino-L-alanine and L-alpha-aminoadipate) inhibit the uptake of glutamate into  glial cells, and that at least one of these may block the conversion of glutamate into glutamine and glutathione in these cells. (McBean, 1994a,b; McBean et al., 1995).  b-N-oxalylamino-L-alanine has been shown to produce symptoms of Motor Neurone Disease in humans, and a full understanding of the metabolic interrelationships between neurones and glial cells is clearly important for determining how these toxins act. In this study we intend to undertake a detailed examination of the pathways of alanine utilisation and formation in astrocytes (glial cells), and the effects of gliotoxins thereon.

Impact of the gliotoxin L-serine-O-sulphate on cellular metabolism in cultured rat astrocytes. Brennan L, Alves PM, Hewage C, Malthouse JP, McBean GJ.Neurochem Int. 2006 Jun;48(8):739-45.

Brennan, L., Hewage,C., Malthouse,J.P.G. and McBean, G.(2004). Gliotoxins disrupt alanine metabolism and glutathione production in C6 glioma cells: a 13C-NMR spectroscopic study. Neurochem International 45, 1155-1165.

Brennan,L., Hewage, C., Malthouse, J.P.G. and McBean, G.J. (2003).
An NMR study of alterations in [1-13C]glucose metabolism in C6 glioma cells by gliotoxic amino acids.  Neurochemistry International, 42, 441-448

McBean, G.J. (1994a) Inhibition of the glutamate transporter and glial enzymes in rat striatum by the gliotoxin, aminoadipate. Br. J. Pharmacol. 113,  536-540

McBean, G.J. (1994b) The effect of L-aminoadipate on rat brain g-glutamylcysteine synthetase. Eur. J. Neurosci. 5 (Suppl.6), P159.

McBean, G.J., Doorty, K.B., Tipton, K.F. and Kollegger, H. (1995) Alteration in the glial cell metabolism of glutamate by kainate and N-methyl-D-aspartate.  Toxicon 33 , 569-576.
 
 





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